Lung‐Yi Loey Mak, Tsung‐Hui Hu, Desmond Y. H. Yap
BACKGROUND: Renal safety is an important consideration for treatment selection in chronic hepatitis B (CHB) because of the ageing population and increasing prevalence of medical comorbidities. However, the renal safety profiles of first-line nucleos(t)ide analogues (NUCs) for CHB-tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and entecavir (ETV) have not been comprehensively reviewed. AIMS: To evaluate the renal safety of ETV, TDF, and TAF in general and special populations with CHB. METHODS: In this narrative review, relevant studies in PubMed were identified using a range of keywords, followed by manual screening of reference lists to capture additional sources. RESULTS: Based on current randomised and real-world evidence, TDF may cause more nephrotoxic effects than ETV in patients with pre-existing moderate-to-severe chronic kidney disease (CKD), but the two agents may have similar renal safety profiles among patients with no or mild baseline renal impairment. Randomised data showed that TAF is significantly less nephrotoxic than TDF in different clinical settings. Retrospective data from both treatment-naïve and -experienced patients, as well as special populations, including patients with renal impairment, kidney transplant, advanced age, and acute-on-chronic liver failure, indicated that TAF may be more likely to improve renal function compared to ETV. CONCLUSIONS: Current first-line NUCs show comparable renal safety profiles in CHB patients with no or mild kidney dysfunction, with growing evidence that favours TAF. Future prospective studies are needed to validate these findings, and more research should focus on CHB patients with diabetes mellitus who are at risk of CKD.